1. Field of the Invention
This invention relates to sustained absorption pharmaceutical compositions and, in particular, to a sustained absorption theophylline composition.
2. Description of the Prior Art
Theophylline (1,3-dimethylxanthine) has a pharmacological activity similar to that of the other xanthine derivatives, caffeine and theobromine. The diuretic action of theophylline though stronger than that of caffeine is of short duration. Theophylline is a more powerful relaxant of involuntary muscle than either theobromine or caffeine. Theophylline is primarily used as a bronchosphasm relaxant or bronchodilator in bronchosphasm associated with asthma, chronic bronchitis and emphysema.
Theophylline has been found to have a minimum effective plasma concentration of about 5 mcg/ml and an average therapeutic concentration of about 10 mcg/ml. The therapeutic range of concentration of theophylline is generally regarded in practice as 10-20 mcg/ml, levels below 10 mcg/ml being ineffective and levels above 20 mcg/ml being toxic.
The apparent biological half-life of theophylline has been found to range from 4-9 hours.
Preparations of anhydrous theophylline require a dosage regimen of 150-500 mg orally every six hours for adults.
For this reason, a number of slow or sustained release forms of theophylline have been developed and include: THEOGRAD, which is marketed by Abbott Laboratories Limited and comes in 350 mg tablets and is administered at a rate of one tablet per 12 hours; THEO-DUR, marketed by Fisons Limited and which comes in 200 mg and 300 mg tablets and is administered 12 hourly, initially 200-300 mg, increasing by 100-150 mg until a sufficient therapeutic effect is obtained; and UNIPHYLLIN UNICONTIN, marketed by Napp Laboratories Limited which comes in 200 mg tablets, with three or four tablets being taken as a single daily dose, following initial therapy of two daily given as a once or twice daily dosage with subsequent increments as necessary until a sufficient therapeutic effect is obtained.
With each slow-release form of theophylline the dose is increased until the required therapeutic effect is obtained, this is known as a titration standard.
An effective slow or sustained release form of theophylline suitable for once daily administration must be capable of maintaining the plasma concentration of theophylline within the range of 10-20 mcg/ml over 24 hours. Only a product with a Cmax/Cmin at 24 hours ratio of 2:1 or less could maintain levels within this range 24 hours after administration.
It is an object of the present invention to provide a sustained absorption form of theophylline which is suitable for once daily administration and which gives a consistent Cmax/Cmin ratio at 24 hours of 2:1 or less.